Aluminum complexes and their use in the synthesis of cyclic carbonates

ABSTRACT

Dimeric aluminium catalysts of formula I: and their use in catalysing the synthesis of cyclic carbonates from epoxides and carbon dioxide.

The present invention relates to aluminium(acen) and aluminium (salacen)complexes and their use as catalysts for synthesising cyclic carbonatesfrom epoxides and carbon dioxide.

Cyclic carbonates are commercially important products currentlymanufactured on a multi-tonne scale for use as polar aprotic solvents,additives, antifoam agents for anti-freeze, plasticisers, and monomersfor polymer synthesis (see Darensbourg, et al., Coord. Chem. Rev., 153(1996), 155-174; Coates, et al., Angew. Chem. Int. Ed., 43 (2004),6618-6639; Zevenhoven et al. Cat. Today 2006, 115, 73-79).

The synthesis of cyclic carbonates generally involves the reaction ofepoxides with carbon dioxide, and hence could be used to sequestratecarbon dioxide, thus reducing the level of greenhouse gases in theatmosphere.

Catalysts for the synthesis of cyclic carbonates from epoxides andcarbon dioxide are known in the art (see Darensbourg, et al., Coord.Chem. Rev., 153 (1996), 155-174; Yoshida, et al., Chem. Eur. J., 10(2004), 2886-2893; Sun, et al., J. Organomet. Chem., 690 (2005),3490-3497) although these require elevated reaction temperatures and/orhigh pressures of carbon dioxide, the reaction often being conducted insupercritical carbon dioxide (see Lu, et al., App. Cat. A, 234 (2002),25-33).

Ratzenhofer, et al., (Angew. Chemie Int. Ed. Engl., 19 (1980), 317-318)succeeded in carrying out the reaction between 2-methyloxirane andcarbon dioxide at room temperature and atmospheric pressure usingcatalysts consisting of a mixture of a metal halide and a Lewis base.However, a long reaction time of 7 days was required. Kisch, et al.,(Chem. Ber., 119 (1986), 1090-1094), carrying out the same reactionunder the same conditions and also using catalysts of this type, reportsa reaction time of 3.5 to 93 hours using up to 4 mol % of a ZnCl₂catalyst and up to 16 mol % of a (nButyl)₄NI catalyst.

Lu, et al., (J. Mol. Cat. A, 210 (2004), 31-34; J. Cat., 227 (2004),537-541) describe the use of tetradentate Schiff-base aluminiumcomplexes in conjunction with a quaternary ammonium salt or polyether-KYcomplexes as catalyst systems for the reaction of various epoxides withcarbon dioxide at room temperature and about 6 atmospheres.

Metal(salen) complexes, including aluminium(salen) complexes, arewell-known in the art for their use as catalysts. Lu, et al., App. Cat.A, 234 (2002), 25-33, describes the use of a monomeric aluminium(salen)catalyst.

Also known in the art is the method of synthesising aluminium(salen)catalysts by treating a salen ligand with Me₃Al, Et₃Al, Me₂AlCl,Me₂AlOTf, Et₂AlBr or Et₂AlCl in a two-stage process (reviewed in Atwoodand Harvey, Chem. Rev., 2001, 101, 37-52).

The present inventor has previously found that, in the presence of atetraalkylammonium halide cocatalyst, dimeric aluminium(salen) complexesare highly active catalysts for the reaction of epoxides with carbondioxide to produce cyclic carbonates, and allow the reaction to becarried out at room temperature and atmospheric pressure, using shortreaction times and commercially viable amounts of catalyst, as describedin Melendez, J., et al., Eur J. Inorg Chem, 2007, 3323-3326 and WO2008/132474. In copending application PCT/GB2009/000624, the presentinventor has also discovered that the cocatalyst can be combined intothe catalyst molecule, and that the combined catalysts and co-catalystcan be immobilised on a solid support.

The present inventor has now found that it is possible to simplify thestructure of the catalyst. The catalysts disclosed below have cheaperstarting materials (e.g. acetylacetone), and the starting materials aremore readily available.

Accordingly a first aspect of the invention provides a dimeric aluminiumcatalyst of formula I:

wherein:

-   a) each of the substituents R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰,    R¹¹ and R¹², is independently selected from H, halo, optionally    substituted C₁₋₂₀ alkyl (including CAr₃, where Ar is a C₅₋₂₀ aryl    group), optionally substituted C₅₋₂₀ aryl, optionally substituted    C₃₋₂₀ heterocyclyl, ether and nitro, where R², R⁵, R⁸ and R¹¹ may    additionally be independently selected from optionally substituted    ester or optionally substituted acyl or the pairs of R² and R³, R⁵    and R⁶, R⁸ and R⁹ and R¹¹ and R¹² may independently together form a    C₂₋₄ alkylene chain, optionally substituted by one or more groups    selected from C₁₋₄ alkyl and C₅₋₇ aryl; or-   b) R⁵ and R⁶ together with the carbon atoms to which they are    attached form an optionally substituted benzene ring of formula:

and

-   -   R¹¹ and R¹² together with the carbon atoms to which they are        attached form an optionally substituted benzene ring of formula:

-   -   each of the substituents R¹, R², R³, R⁴, R⁷, R⁸, R⁹, R¹⁰, R¹³,        R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰, is independently selected        from H, halo, optionally substituted C₁₋₂₀ alkyl (including        CAr₃, where Ar is a C₅₋₂₀ aryl group), optionally substituted        C₅₋₂₀ aryl, optionally substituted C₃₋₂₀ heterocyclyl, ether and        nitro;        X¹ and X² are independently either (i) a C₂₋₅ alkylene chain,        which is optionally substituted by one or more groups selected        from C₁₋₄ alkyl and C₅₋₇ aryl, or a C₁₋₃ bisoxyalkylene chain,        which is optionally substituted by one or more groups selected        from C₁₋₄ alkyl and C₅₋₇ aryl or (ii) represent a divalent group        selected from C₅₋₇ arylene, C₉₋₁₀ arylene, bi-C₅₋₇ aryl,        bi-C₉₋₁₀ aryl, C₅₋₇ cyclic alkylene and C₃₋₇ heterocyclylene,        which may be optionally substituted.

In a second aspect, the present invention provides a catalyst defined inthe first aspect of the invention, except that:

-   (i) (a) at least one of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰,    R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰ (where present)    is selected from L-A, where L is a single bond or a C₁₋₁₀ alkylene    group and A is an onium group paired with a counterion selected from    Cl, Br and I; and/or    -   (b) at least one of X¹ and X² is a divalent C₃₋₇ heterocyclene        group, containing a ring atom which is a quaternary nitrogen        forming part of an ammonium group paired with a counterion        selected from Cl, Br and I; and/or    -   (c) at least one of X¹ and X² is a C₂₋₅ alkylene chain or a C₁₋₃        bisoxyalkylene chain, substituted by a group -Q-L-A, where Q is        either —C(═O)—O—, —C(═O)—NH—, or a single bond; and/or    -   (d) at least one of R², R⁵, R⁸ and R¹¹ is -Q′-L-A, where Q′ is        either —C(═O)—O— or —C(═O)—;        and/or-   (ii) (a) one of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹²,    R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰ (where present) is L-A′,    where L is as defined above and A′ is an onium linking group bound    to a solid support and paired with a counterion selected from Cl, Br    and I; or    -   (b) one of X¹ and X² is a divalent C₃₋₇ heterocyclene group,        containing a ring atom which is a quaternary nitrogen forming        part of an ammonium linking group bound to a solid support and        paired with a counterion selected from Cl, Br and I; or    -   (c) one of X¹ and X² is a C₂₋₅ alkylene chain or a C₁₋₃        bisoxyalkylene chain, substituted by a group -Q-L-A′; or    -   (d) one of R², R⁵, R⁸ and R¹¹ is -Q′-L-A′.

Thus, in catalysts of the second aspect, when the catalyst is covalentlybound to a solid support, only one linking group to the solid support ispresent. However, one or more ammonium groups/quaternary nitrogen atomsmay be present.

The catalysts of the first aspect or the second aspect where: (a) atleast one of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³,R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰ (where present) is selected fromL-A; and/or (b) at least one of X¹ and X² is a divalent C₃₋₇heterocyclene group, containing a ring atom which is a quaternarynitrogen atom forming part of an ammonium group; and/or (c) at least oneof X¹ and X² is a C₂₋₅ alkylene chain or a C₁₋₃ bisoxyalkylene chain,substituted by a group -Q-L-A, where Q is either —C(═O)—O—, —C(═O)—, NHor a single bond and/or (d) at least one of R², R⁵, R⁸ and R¹¹ is-Q′-L-A, where Q′ is either —C(═O)—O— or —C(═O)—, may be immobilized ona solid support, either by the use of steric effects or by electrostaticbinding.

If the catalyst of the first or second aspects includes one or morechiral centres, then it may be a (wholly or partially) racemic mixtureor other mixture thereof, for example, a mixture enriched in oneenantiomer or diastereoisomer, a single enantiomer or diastereoisomer,or a mixture of the stereoisomers. Methods for the preparation (e.g.,asymmetric synthesis) and separation (e.g., fractional crystallisationand chromatographic means) of such isomeric forms are either known inthe art or are readily obtained by adapting the methods taught herein,or known methods, in a known manner. Preferably the catalyst of thefirst and second aspects is a single enantiomer, if a chiral centre ispresent.

In some embodiments, it is preferred that the catalysts are symmetrical,i.e. that the two aluminium ligands are the same. Therefore, it may bepreferred that X¹═X², R¹═R⁷, R²═R⁸, R³═R⁹, R⁴═R¹⁰, R⁵═R¹¹, R⁶═R¹² and(if present) R¹³═R¹⁷, R¹⁴═R¹⁸, R¹⁵═R¹⁹ and R¹⁶═R²⁰.

A third aspect of the present invention provides a process for theproduction of cyclic carbonates comprising contacting an epoxide withcarbon dioxide in the presence of a dimeric aluminium(acen) oraluminium(salacen) catalyst according to the first aspect of theinvention in combination with a co-catalyst capable of supplying Y⁻,where Y is selected from Cl, Br and I; or in the presence of a dimericaluminium(acen) or aluminium(salacen) catalyst according to the secondaspect of the invention.

The cocatalyst is preferably soluble in the reaction mixture. Suitablesources of Y⁻ are MY, where M is a suitable cation, such as oniumhalides, which include, but are not limited to, R₄NY, R₃SY, R₄PY andR₄SbY, where each R is independently selected from optionallysubstituted C₁₋₁₀ alkyl, C₃₋₂₀ heterocyclyl and C₅₋₂₀ aryl groups andone R can be an acyl group, and simple halides, e.g. NaCl, Kl.

The reaction of the third aspect may be defined as follows:

wherein R^(C3) and R^(C4) are independently selected from H, optionallysubstituted C₁₋₁₀ alkyl, optionally substituted C₃₋₂₀ heterocyclyl andoptionally substituted C₅₋₂₀ aryl, or R^(C3) and R^(C4) form anoptionally substituted linking group between the two carbon atoms towhich they are respectively attached. The linking group, together withthe carbon atoms to which it is attached, may form an optionallysubstituted C₅₋₂₀ cycloalkyl or C₅₋₂₀ heterocyclyl group. The C₅₋₂₀cycloalkyl or C₅₋₂₀ heterocyclyl group may be substituted only in asingle position on the ring, for example, adjacent the epoxide. Suitablesubstituents, include optionally substituted C₁₋₁₀ alkyl, optionallysubstituted C₃₋₂₀ heterocyclyl and optionally substituted C₅₋₂₀ aryl.

A possible substituent for the C₁₋₁₀ alkyl group is a C₅₋₂₀ aryl group.

The third aspect of the invention also provides the use of a dimericaluminium(acen) or aluminium (salacen)) catalyst of the first aspect ofthe invention in combination with a co-catalyst capable of supplying Y⁻,or a dimeric aluminium(acen) or aluminium(salacen) catalyst of thesecond aspect of the invention for the production of cyclic carbonatesfrom epoxides.

A fourth aspect of the invention provides a process for the synthesis ofa dimeric aluminium(acen) or aluminium(salacen) catalyst of formula Iaccording to the first or second aspects of the invention.

DETAILED DESCRIPTION OF THE INVENTION Definitions

Epoxide: The term “epoxide”, as used herein, may pertain to a compoundof the formula:

wherein R^(C3) and R^(C4) are independently selected from H, optionallysubstituted C₁₋₁₀ alkyl, optionally substituted C₃₋₂₀ heterocyclyl andoptionally substituted C₅₋₂₀ aryl, or R^(C3) and R^(C4) form anoptionally substituted linking group between the two carbon atoms towhich they are respectively attached. The linking group, together withthe carbon atoms to which it is attached, may form an optionallysubstituted C₅₋₂₀ cycloalkyl or C₅₋₂₀ heterocylyl group. The C₅₋₂₀cycloalkyl or C₅₋₂₀ heterocylyl group may be substituted only in asingle position on the ring, for example, adjacent the epoxide. Suitablesubstituents, include optionally substituted C₁₋₁₀ alkyl, optionallysubstituted C₃₋₂₀ heterocyclyl and optionally substituted C₅₋₂₀ aryl.

The optional substituents may be selected from: C₁₋₁₀ alkyl, C₃₋₂₀heterocyclyl, C₅₋₂₀ aryl, halo, hydroxy, ether, cyano, nitro, carboxy,ester, amido, amino, acylamido, ureido, acyloxy, thiol, thioether,sulfoxide, sulfonyl, thioamido and sulfonamino.

In some embodiments, the C₁₋₁₀ alkyl group is substituted by a C₅₋₂₀aryl group.

Preferably, the epoxide is a terminal epoxide, i.e. R^(C4)═H.

In some embodiments, R^(C3) is selected from optionally substituted C₁₋₄alkyl and optionally substituted C₅₋₇ aryl. In some of these embodimentsR^(C3) is unsubstituted.

Preferred epoxides are ethylene oxide (R^(C3)═R^(C4)═H), propylene oxide(R^(C3)=methyl, R^(C4)═H) butylene oxide (R^(C3)=ethyl, R^(C4)═H), andstyrene oxide (R^(C3)=phenyl, R^(C4)═H).

Cyclic carbonate: the term “cyclic carbonate”, as used herein, maypertain to a compound of the formula:

wherein R^(C3) and R^(C4) are as defined above.

Solid support: Catalysts of the present invention may be immobilized ona solid support by:

(a) covalent binding (those where one of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸,R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰ (ifpresent) is selected from L-A′ or one of X¹ and X² contains a quaternarynitrogen forming part of an ammonium linking group);(b) steric trapping; or(c) electrostatic binding.

These various methods are reviewed by Carlos Baleizão and HermenegildoGarcia in “Chiral Salen Complexes: An Overview to Recoverable andReusable Homogeneous and Heterogeneous Catalysts” (Chem. Rev. 2006, 106,3987-4043).

For covalent binding, the solid support needs to contain or bederivatized to contain reactive functionalities which can serve forcovalently linking a compound to the surface thereof. Such materials arewell known in the art and include, by way of example, silicon dioxidesupports containing reactive Si—OH groups, polyacrylamide supports,polystyrene supports, polyethyleneglycol supports, and the like. Afurther example is sol-gel materials. Silica can be modified to includea 3-chloropropyloxy group by treatment with(3-chloropropyl)triethoxysilane. Another example is Al pillared clay,which can also be modified to include a 3-chloropropyloxy group bytreatment with (3-chloropropyl)triethoxysilane. Such supports willpreferably take the form of small beads, pins/crowns, laminar surfaces,pellets or disks. They may also take the form of powders. Solid supportsfor covalent binding of particular interest in the present inventioninclude siliceous MCM-41 and MCM-48 (modified with 3-chloropropylgroups), ITQ-2 and amorphous silica, SBA-15 and hexagonal mesoporoussilica. Also of particular interest are sol-gels. Other conventionalforms may also be used.

For steric trapping, the most suitable class of solid support iszeolites, which may be natural or modified. The pore size must besufficiently small to trap the catalyst but sufficiently large to allowthe passage of reactants and products to and from the catalyst. Suitablezeolites include zeolites X, Y and EMT as well as those which have beenpartially degraded to provide mesopores, that allow easier transport ofreactants and products.

For the electrostatic binding of the catalyst to a solid support,typical solid supports may include silica, Indian clay, Al-pillaredclay, Al-MCM-41, K10, laponite, bentonite, and zinc-aluminium layereddouble hydroxide. Of these silica and montmorillonite clay are ofparticular interest.

Alkyl: The term “alkyl”, as used herein, pertains to a monovalent moietyobtained by removing a hydrogen atom from a carbon atom of a hydrocarbonhaving from 1 to 20 carbon atoms (unless otherwise specified), which maybe aliphatic or alicyclic and which may be saturated or unsaturated(e.g. partially saturated, fully unsaturated). Thus, the term “alkyl”includes the sub-classes alkenyl, alkynyl, cycloalkyl, cycloalkenyl,cycloalkynyl, etc., as discussed below.

Alkylene: The term “alkylene”, as used herein, pertains to a divalentmoiety obtained by removing two hydrogen atoms from one or two carbonatoms of a hydrocarbon having from 1 to 20 carbon atoms (unlessotherwise specified), which may be aliphatic or alicyclic and which maybe saturated or unsaturated (e.g. partially saturated, fullyunsaturated). Thus, the term “alkylene” includes the sub-classesalkenylene, alkynylene, cycloalkylene, cycloalkenylene, cycloalkynylene,etc., as discussed below.

In the context of alkyl and alkylene groups, the prefixes (e.g. C₁₋₄,C₁₋₇, C₁₋₂₀, C₂₋₇, C₃₋₇, etc.) denote the number of carbon atoms, or therange of number of carbon atoms. For example, the term “C₁₋₄ alkyl”, asused herein, pertains to an alkyl group having from 1 to 4 carbon atoms.Examples of groups of alkyl groups include C₁₋₄ alkyl (“lower alkyl”),C₁₋₇ alkyl and C₁₋₂₀ alkyl. Note that the first prefix may varyaccording to other limitations; for example, for unsaturated alkylgroups, the first prefix must be at least 2; for cyclic alkyl groups,the first prefix must be at least 3; etc. For example, the term “C₁₋₇alkylene”, as used herein, pertains to an alkylene group having from 1to 7 carbon atoms.

Examples of (unsubstituted) saturated alkyl groups include, but are notlimited to, methyl (C₁), ethyl (C₂), propyl (C₃), butyl (C₄), pentyl(C₅), hexyl (C₆), and heptyl (C₇).

Examples of (unsubstituted) saturated linear alkyl groups include, butare not limited to, methyl (C₁), ethyl (C₂), n-propyl (C₃), n-butyl(C₄), n-pentyl (amyl) (C₅), n-hexyl (C₆), and n-heptyl (C₇).

Examples of (unsubstituted) saturated branched alkyl groups includeiso-propyl (C₃), iso-butyl (C₄), sec-butyl (C₄), ten-butyl (C₄),iso-pentyl (C₅), and neo-pentyl (C₅).

Examples of (unsubstituted) saturated alkylene groups include, but arenot limited to, methylene (C₁), ethylene (C₂), propylene (C₃), butylene(C₄), pentylene (C₅), hexylene (C₆), and heptylene (C₇).

Examples of (unsubstituted) saturated linear alkylene groups include,but are not limited to, methylene (C₁), ethylene (C₂), n-propylene (C₃),n-butylene (C₄), n-pentylene (amylene) (C₅), n-hexylene (C₆), andn-heptylene (C₇).

Examples of (unsubstituted) saturated branched alkyl groups includeiso-propylene (C₃), iso-butylene (C₄), sec-butylene (C₄), tert-butylene(C₄), iso-pentylene (C₅), and neo-pentylene (C₅).

Alkenyl: The term “alkenyl”, as used herein, pertains to an alkyl grouphaving one or more carbon-carbon double bonds. Examples of groups ofalkenyl groups include C₂₋₄ alkenyl, C₂₋₇ alkenyl, C₂₋₂₀ alkenyl.

Examples of (unsubstituted) unsaturated alkenyl groups include, but arenot limited to, ethenyl (vinyl, —CH═CH₂), 1-propenyl (—CH═CH—CH₃),2-propenyl (allyl, —CH₂—CH═CH₂), isopropenyl (1-methylvinyl,—C(CH₃)═CH₂), butenyl (C₄), pentenyl (C₅), and hexenyl (C₆).

Alkenylene: The term “alkenylene”, as used herein, pertains to analkylene group having one or more carbon-carbon double bonds. Examplesof groups of alkenylene groups include C₂₋₄ alkenylene, C₂₋₇ alkenylene,C₂₋₂₀ alkenylene.

Alkynyl: The term “alkynyl”, as used herein, pertains to an alkyl grouphaving one or more carbon-carbon triple bonds. Examples of groups ofalkynyl groups include C₂₋₄ alkynyl, C₂₋₇ alkynyl, C₂₋₂₀ alkynyl.

Examples of (unsubstituted) unsaturated alkynyl groups include, but arenot limited to, ethynyl (ethinyl, —C≡CH) and 2-propynyl (propargyl,—CH₂—C≡CH).

Alkynylene: The term “alkynyl”, as used herein, pertains to an alkylenegroup having one or more carbon-carbon triple bonds. Examples of groupsof alkynylene groups include C₂₋₄ alkynylene, C₂₋₇ alkynylene, C₂₋₂₀alkynylene.

Cycloalkyl: the term “cycloalkyl”, as used herein, pertains to an alkylgroup which is also a cyclyl group; that is, a monovalent moietyobtained by removing a hydrogen atom from an alicyclic ring atom of acarbocyclic ring of a carbocyclic compound, which carbocyclic ring maybe saturated or unsaturated (e.g. partially unsaturated, fullyunsaturated), which moiety has from 3-20 carbon atoms (unless otherwisespecified), including from 3 to 20 ring atoms. Thus, the term“cycloalkyl” includes the sub-classes cycloalkenyl and cycloalkynyl.Preferably, each ring has from 3 to 7 ring atoms. Examples of groups ofcycloalkyl groups include C₃₋₂₀ cycloalkyl, C₃₋₁₅ cycloalkyl, C₃₋₁₀cycloalkyl, C₃₋₇ cycloalkyl.

Cycloalkylene: the term “cycloalkylene”, as used herein, pertains to analkylene group which is also a cyclyl group; that is, a divalent moietyobtained by removing two hydrogen atoms from one or two alicyclic ringatoms of a carbocyclic ring of a carbocyclic compound, which carbocyclicring may be saturated or unsaturated (e.g. partially unsaturated, fullyunsaturated), which moiety has from 3-20 carbon atoms (unless otherwisespecified), including from 3 to 20 ring atoms. Thus, the term“cycloalkylene” includes the sub-classes cycloalkenylene andcycloalkynylene. Preferably, each ring has from 3 to 7 ring atoms.Examples of groups of cycloalkylene groups include C₃₋₂₀ cycloalkylene,C₃₋₁₅ cycloalkylene, C₃₋₁₀ cycloalkylene, C₃₋₇ cycloalkylene.

Cyclic alkylene: The term “cyclic alkylene” as used herein pertains to adivalent moiety obtained by removing a hydrogen atom from each of twoadjacent alicyclic ring atoms of a carbocyclic ring of a carbocycliccompound, which carbocyclic ring may be saturated or unsaturated (e.g.partially saturated, fully unsaturated), which moiety has from 3 to 20carbon atoms (unless otherwise specified), including from 3 to 20 ringatoms. Preferably each ring has from 5 to 7 ring atoms. Examples ofgroups of cyclic alkylene groups include C₃₋₂₀ cyclic alkylenes, C₃₋₁₅cyclic alkylenes, C₃₋₁₀ cyclic alkylenes, C₃₋₇ cyclic alkylenes.

Examples of cycloalkyl groups and cyclic alkylene groups include, butare not limited to, those derived from:

-   -   saturated monocyclic hydrocarbon compounds:        cyclopropane (C₃), cyclobutane (C₄), cyclopentane (C₅),        cyclohexane (C₆), cycloheptane (C₇), methylcyclopropane (C₄),        dimethylcyclopropane (C₅), methylcyclobutane (C₅),        dimethylcyclobutane (C₆), methylcyclopentane (C₆),        dimethylcyclopentane (C₇), methylcyclohexane (C₇),        dimethylcyclohexane (C₈), menthane (C₁₀);    -   unsaturated monocyclic hydrocarbon compounds: cyclopropene (C₃),        cyclobutene (C₄), cyclopentene (C₅), cyclohexene (C₆),        methylcyclopropene (C₄), dimethylcyclopropene (C₅),        methylcyclobutene (C₅), dimethylcyclobutene (C₆),        methylcyclopentene (C₆), dimethylcyclopentene (C₇),        methylcyclohexene (C₇), dimethylcyclohexene (C₈);    -   saturated polycyclic hydrocarbon compounds:        thujane (C₁₀), carane (C₁₀), pinane (C₁₀), bornane (C₇),        norcarane (C₇), norpinane (C₇), norbornane (C₇), adamantane        (C₁₀), decalin (decahydronaphthalene) (C₁₀);    -   unsaturated polycyclic hydrocarbon compounds:        camphene (C₁₀), limonene (C₁₀), pinene (C₁₀);    -   polycyclic hydrocarbon compounds having an aromatic ring:        indene (C₉), indane (e.g., 2,3-dihydro-1H-indene) (C₉), tetralin        (1,2,3,4-tetrahydronaphthalene) (C₁₀), acenaphthene (C₁₂),        fluorene (C₁₃), phenalene (C₁₃), acephenanthrene (C₁₅),        aceanthrene (C₁₆), cholanthrene (C₂₀).

Heterocyclyl: The term “heterocyclyl”, as used herein, pertains to amonovalent moiety obtained by removing a hydrogen atom from a ring atomof a heterocyclic compound, which moiety has from 3 to 20 ring atoms(unless otherwise specified), of which from 1 to 10 are ringheteroatoms. Preferably, each ring has from 3 to 7 ring atoms, of whichfrom 1 to 4 are ring heteroatoms.

Heterocyclylene: The term “heterocyclylene”, as used herein, pertains toa divalent moiety obtained by removing a hydrogen atom from each of twoadjacent ring atoms of a heterocyclic compound, which moiety has from 3to 20 ring atoms (unless otherwise specified), of which from 1 to 10 arering heteroatoms. Preferably, each ring has from 3 to 7 ring atoms, ofwhich from 1 to 4 are ring heteroatoms.

The heterocyclyl or heterocyclylene group may be bonded via carbon orhetero ring atoms. Preferably, the heterocyclylene group is bonded viatwo carbon atoms.

When referring to heterocyclyl or heterocyclylene groups, the prefixes(e.g. C₃₋₂₀, C₃₋₇, C₅₋₆, etc.) denote the number of ring atoms, or rangeof number of ring atoms, whether carbon atoms or heteroatoms. Forexample, the term “C₅₋₆ heterocyclyl”, as used herein, pertains to aheterocyclyl group having 5 or 6 ring atoms. Examples of groups ofheterocyclyl groups include C₃₋₂₀ heterocyclyl, C₅₋₂₀ heterocyclyl,C₃₋₁₅ heterocyclyl, C₅₋₁₅ heterocyclyl, C₃₋₁₂ heterocyclyl, C₅₋₁₂heterocyclyl, C₃₋₁₀ heterocyclyl, C₅₋₁₀ heterocyclyl, C₃₋₇ heterocyclyl,C₅₋₇ heterocyclyl, and C₅₋₆ heterocyclyl.

Similarly, the term “C₅₋₆ heterocyclylene”, as used herein, pertains toa heterocyclylene group having 5 or 6 ring atoms. Examples of groups ofheterocyclylene groups include C₃₋₂₀ heterocyclylene, C₅₋₂₀heterocyclylene, C₃₋₁₅ heterocyclylene, C₅₋₁₅ heterocyclylene, C₃₋₁₂heterocyclylene, C₅₋₁₂ heterocyclylene, C₃₋₁₀ heterocyclylene, C₅₋₁₀heterocyclylene, C₃₋₇ heterocyclylene, C₅₋₇ heterocyclylene, and C₅₋₆heterocyclylene.

Examples of monocyclic heterocyclyl and heterocyclylene groups include,but are not limited to, those derived from:

N₁: aziridine (C₃), azetidine (C₄), pyrrolidine (tetrahydropyrrole)(C₅), pyrroline (e.g., 3-pyrroline, 2,5-dihydropyrrole) (C₅), 2H-pyrroleor 3H-pyrrole (isopyrrole, isoazole) (C₅), piperidine (C₆),dihydropyridine (C₆), tetrahydropyridine (C₆), azepine (C₇);O₁: oxirane (C₃), oxetane (C₄), oxolane (tetrahydrofuran) (C₅), oxole(dihydrofuran) (C₅), oxane (tetrahydropyran) (C₆), dihydropyran (C₆),pyran (C₆), oxepin (C₇);S₁: thiirane (C₃), thietane (C₄), thiolane (tetrahydrothiophene) (C₅),thiane (tetrahydrothiopyran) (C₆), thiepane (C₇);O₂: dioxolane (C₅), dioxane (C₆), and dioxepane (C₇);O₃: trioxane (C₆);N₂: imidazolidine (C₅), pyrazolidine (diazolidine) (C₅), imidazoline(C₅), pyrazoline (dihydropyrazole) (C₅), piperazine (C₆);N₁O₁: tetrahydrooxazole (C₅), dihydrooxazole (C₅), tetrahydroisoxazole(C₅), dihydroisoxazole (C₅), morpholine (C₆), tetrahydrooxazine (C₆),dihydrooxazine (C₆), oxazine (C₆);N₁S₁: thiazoline (C₅), thiazolidine (C₅), thiomorpholine (C₆);N₂O₁: oxadiazine (C₆);O₁S₁: oxathiole (C₅) and oxathiane (thioxane) (C₆); and,N₁O₁S₁: oxathiazine (C₆).

Examples of substituted (non-aromatic) monocyclic heterocyclyl andheterocyclylene groups include those derived from saccharides, in cyclicform, for example, furanoses (C₅), such as arabinofuranose,lyxofuranose, ribofuranose, and xylofuranse, and pyranoses (C₆), such asallopyranose, altropyranose, glucopyranose, mannopyranose, gulopyranose,idopyranose, galactopyranose, and talopyranose.

C₅₋₂₀ aryl: The term “C₅₋₂₀ aryl”, as used herein, pertains to amonovalent moiety obtained by removing a hydrogen atom from an aromaticring atom of a C₅₋₂₀ aromatic compound, said compound having one ring,or two or more rings (e.g., fused), and having from 5 to 20 ring atoms,and wherein at least one of said ring(s) is an aromatic ring.Preferably, each ring has from 5 to 7 carbon atoms.

The ring atoms may be all carbon atoms, as in “carboaryl groups” inwhich case the group may conveniently be referred to as a “C₅₋₂₀carboaryl” group.

C₅₋₂₀ arylene: The term “C₅₋₂₀ arylene”, as used herein, pertains to adivalent moiety obtained by removing a hydrogen atom from each of twoadjacent ring atoms of a C₅₋₂₀ aromatic compound, said compound havingone ring, or two or more rings (e.g., fused), and having from 5 to 20ring atoms, and wherein at least one of said ring(s) is an aromaticring. Preferably, each ring has from 5 to 7 carbon atoms.

The ring atoms may be all carbon atoms, as in “carboarylene groups” inwhich case the group may conveniently be referred to as a “C₅₋₂₀carboarylene” group.

Examples of C₅₋₂₀ aryl and C₅₋₂₀ arylene groups which do not have ringheteroatoms (i.e. C₅₋₂₀ carboaryl and C₅₋₂₀ carboarylene groups)include, but are not limited to, those derived from benzene (i.e.phenyl) (C₆), naphthalene (C₁₀), anthracene (C₁₄), phenanthrene (C₁₄),and pyrene (C₁₆).

Alternatively, the ring atoms may include one or more heteroatoms,including but not limited to oxygen, nitrogen, and sulfur, as in“heteroaryl groups” or “heteroarylene groups”. In this case, the groupmay conveniently be referred to as a “C₅₋₂₀ heteroaryl” or “C₅₋₂₀heteroarylene” group, wherein “C₅₋₂₀” denotes ring atoms, whether carbonatoms or heteroatoms. Preferably, each ring has from 5 to 7 ring atoms,of which from 0 to 4 are ring heteroatoms.

The heteroaryl or heteroarylene group may be bonded via carbon or heteroring atoms. Preferably, the heteroarylene group is bonded via two carbonatoms.

Examples of C₅₋₂₀ heteroaryl and C₅₋₂₀ heteroarylene groups include, butare not limited to, C₅ heteroaryl and C₅ heteroarylene groups derivedfrom furan (oxole), thiophene (thiole), pyrrole (azole), imidazole(1,3-diazole), pyrazole (1,2-diazole), triazole, oxazole, isoxazole,thiazole, isothiazole, oxadiazole, tetrazole and oxatriazole; and C₆heteroaryl groups derived from isoxazine, pyridine (azine), pyridazine(1,2-diazine), pyrimidine (1,3-diazine; e.g., cytosine, thymine,uracil), pyrazine (1,4-diazine) and triazine.

Examples of C₅₋₂₀ heteroaryl and C₅₋₂₀ heteroarylene groups whichcomprise fused rings, include, but are not limited to, C₉ heteroaryl andC₉ heteroarylene groups derived from benzofuran, isobenzofuran,benzothiophene, indole, isoindole; C₁₀heteroaryl and C₁₀ heteroarylenegroups derived from quinoline, isoquinoline, benzodiazine,pyridopyridine; C₁₄ heteroaryl and C₁₄ heteroarylene groups derived fromacridine and xanthene.

Bi-C₅₋₂₀ aryl: The term “bi-C₅₋₂₀ aryl”, as used herein, pertains to adivalent moiety obtained by removing a hydrogen atom from two aromaticring atoms of a bi-C₅₋₂₀ aromatic compound, said compound comprising twoC₅₋₂₀ aromatic moieties joined by a single bond, each moiety having onering, or two or more rings (e.g., fused), and having from 5 to 20 ringatoms, and wherein at least one of said ring(s) is an aromatic ring.Preferably, each ring has from 5 to 7 carbon atoms.

The ring atoms may be all carbon atoms, as in “carboaryl groups” inwhich case the group may conveniently be referred to as a “C₅₋₂₀carboaryl” group. Examples of bi-C₅₋₂₀ aryl groups which do not havering heteroatoms (i.e. bi-C₅₋₂₀ carboaryl) include, but are not limitedto, those where both moieties are derived from benzene (i.e.bi-phenyl)(C₆), naphthalene (i.e. bi-naphyhyl)(C₁₀), anthracene (C₁₄),phenanthrene (C₁₄), and pyrene (C₁₆).

Alternatively, the ring atoms of one or both moieties may include one ormore heteroatoms, including but not limited to oxygen, nitrogen, andsulfur, as in “heteroaryl groups” or “heteroarylene groups”. In thiscase, the group may conveniently be referred to as a “bi-C₅₋₂₀heteroaryl” group if both moieties contain ring heteroatoms or a“bi-C₅₋₂₀ carboaryl-C₅₋₂₀ heteroaryl” group if only one moiety comprisesa ring heteroatom. “C₅₋₂₀” denotes ring atoms, whether carbon atoms orheteroatoms. Preferably, each ring has from 5 to 7 ring atoms, of whichfrom 0 to 4 are ring heteroatoms.

A “bi-C₅₋₇ aryl” group is one where both moieties are C₅₋₇ aryl groups.Likewise, a “bi-C₉₋₁₀ aryl” group is one where both moieties are C₉₋₁₀aryl groups

Bisoxy-C₁₋₃ alkylene: —O—(CH₂)_(m)—O—, where m is 1 to 3.

The above alkyl, alkylene, bisoxyalkylene, cyclic alkylene,heterocyclyl, heterocyclylene, aryl, bi-aryl and arylene groups, whetheralone or part of another substituent, may themselves optionally besubstituted with one or more groups selected from themselves and theadditional substituents listed below.

Halo: —F, —Cl, —Br, and —I.

Hydroxy: —OH.

Ether: —OR, wherein R is an ether substituent, for example, a C₁₋₇ alkylgroup (also referred to as a C₁₋₇ alkoxy group), a C₃₋₂₀ heterocyclylgroup (also referred to as a C₃₋₂₀ heterocyclyloxy group), or a C₅₋₂₀aryl group (also referred to as a C₅₋₂₀ aryloxy group), preferably aC₁₋₇ alkyl group.

Nitro: —NO₂.

Cyano (nitrile, carbonitrile): —CN.

Acyl (keto): —C(═O)R, wherein R is an acyl substituent, for example, H,a C₁₋₇ alkyl group (also referred to as C₁₋₇ alkylacyl or C₁₋₇alkanoyl), a C₃₋₂₀ heterocyclyl group (also referred to as C₃₋₂₀heterocyclylacyl), or a C₅₋₂₀ aryl group (also referred to as C₅₋₂₀arylacyl), preferably a C₁₋₇ alkyl group. Examples of acyl groupsinclude, but are not limited to, —C(═O)CH₃ (acetyl), —C(═O)CH₂CH₃(propionyl), —C(═O)C(CH₃)₃ (pivaloyl), and —C(═O)Ph (benzoyl, phenone).

Carboxy (carboxylic acid): —COOH.

Ester (carboxylate, carboxylic acid ester, oxycarbonyl): —C(═O)OR,wherein R is an ester substituent, for example, a C₁₋₇ alkyl group, aC₃₋₂₀ heterocyclyl group, or a C₅₋₂₀ aryl group, preferably a C₁₋₇ alkylgroup. Examples of ester groups include, but are not limited to,—C(═O)OCH₃, —C(═O)OCH₂CH₃, —C(═O)OC(CH₃)₃, and —C(═O)OPh.

Amido (carbamoyl, carbamyl, aminocarbonyl, carboxamide): —C(═O)NR¹R²,wherein R¹ and R² are independently amino substituents, as defined foramino groups. Examples of amido groups include, but are not limited to,—C(═O)NH₂, —C(═O)NHCH₃, —C(═O)N(CH₃)₂, —C(═O)NHCH₂CH₃, and—C(═O)N(CH₂CH₃)₂, as well as amido groups in which R¹ and R², togetherwith the nitrogen atom to which they are attached, form a heterocyclicstructure as in, for example, piperidinocarbonyl, morpholinocarbonyl,thiomorpholinocarbonyl, and piperazinylcarbonyl.

Amino: —NR¹R², wherein R¹ and R² are independently amino substituents,for example, hydrogen, a C₁₋₇alkyl group (also referred to as C₁₋₇alkylamino or di-C₁₋₇ alkylamino), a C₃₋₂₀ heterocyclyl group, or aC₅₋₂₀ aryl group, preferably H or a C₁₋₇alkyl group, or, in the case ofa “cyclic” amino group, R¹ and R², taken together with the nitrogen atomto which they are attached, form a heterocyclic ring having from 4 to 8ring atoms. Examples of amino groups include, but are not limited to,—NH₂, —NHCH₃, —NHCH(CH₃)₂, —N(CH₃)₂, —N(CH₂CH₃)₂, and —NHPh. Examples ofcyclic amino groups include, but are not limited to, aziridinyl,azetidinyl, pyrrolidinyl, piperidino, piperazinyl, perhydrodiazepinyl,morpholino, and thiomorpholino. In particular, the cyclic amino groupsmay be substituted on their ring by any of the substituents definedhere, for example carboxy, carboxylate and amido.

Onium group: —NR₃ (ammonium group), —SR₂, —PR₃ and —SbR₃, where each Ris independently selected from optionally substituted C₁₋₁₀ alkyl, C₃₋₂₀heterocyclyl and C₅₋₂₀ aryl groups and one R can be an acyl group andone or two R can be hydrogen. Two or three of the onium substituents mayjoin together to form cyclic or cage-like structures.

Ammonium group: —NR^(N1)R^(N2)R^(N3), wherein R^(N1), R^(N2) and R^(N3)are independently ammonium substituents, for example, a C₁₋₇ alkylgroup, a C₃₋₂₀ heterocyclyl group, or a C₅₋₂₀ aryl group and where oneor two of R^(N1), R^(N2) and R^(N3) may also be H. One of R^(N1), R^(N2)and R^(N3) may be a C₁₋₃ alkoxy (—(CH₂)₁₋₃—OH) group. Two or three ofthe ammonium substituents may join together to form cyclic or cage-likestructures. Examples of ammonium groups include, but are not limited to,—NH(CH₃)₂, —NH(CH(CH₃)₂)₂, —N(CH₃)₃, —N(CH₂CH₃)₃, and —NH₂Ph.

Onium linking group: —NR₂R′— (ammonium linking group), —SRR′—, —PR₂R′—and —SbR₂R′—, where each R is independently selected from optionallysubstituted C₁₋₁₀ alkyl, C₃₋₂₀ heterocyclyl and C₅₋₂₀ aryl groups andone R can be an acyl group and one or two R can be hydrogen. Two of theonium substituents may join together to form cyclic or cage-likestructures. R′ is a divalent onium substituent, for example, a C₁₋₇alkylene group, a C₃₋₂₀ heterocyclylene group, or a C₅₋₂₀ arylene groupor a divalent C₁₋₃ alkyloxylene (—(CH₂)₁₋₃—O—) group.

Ammonium linking group: —NR^(N1)R^(N2)R^(N4)—, wherein R^(N1) and R^(N2)are independently ammonium substituents, for example, a C₁₋₇ alkylgroup, a C₃₋₂₀ heterocyclyl group, or a C₅₋₂₀ aryl group and where oneor both of R^(N1) and R^(N2) may also be H. The two ammoniumsubstituents may join together to form a cyclic structure. R^(N4) is adivalent ammonium substituent, for example, a C₁₋₇ alkylene group, aC₃₋₂₀ heterocyclylene group, or a C₅₋₂₀ arylene group or a divalent C₁₋₃alkyloxylene (—(CH₂)₁₋₃—O—) group. Examples of ammonium linking groupsinclude, but are not limited to, —NH(CH₃)(CH₂)—,—NH(CH(CH₃)₂)(C(CH₃)₂)—, —N(CH₃)₂(CH₂)—, —N(CH₂CH₃)₂(CH₂CH₂)—, and—NHPh(CH₂)—.

Acylamido (acylamino): —NR¹C(═O)R², wherein R¹ is an amide substituent,for example, hydrogen, a C₁₋₇ alkyl group, a C₃₋₂₀ heterocyclyl group,or a C₅₋₂₀ aryl group, preferably H or a C₁₋₇ alkyl group, mostpreferably H, and R² is an acyl substituent, for example, a C₁₋₇ alkylgroup, a C₃₋₂₀ heterocyclyl group, or a C₅₋₂₀ aryl group, preferably aC₁₋₇ alkyl group. Examples of acylamide groups include, but are notlimited to, —NHC(═O)CH₃, —NHC(═O)CH₂CH₃, and —NHC(═O)Ph. R¹ and R² maytogether form a cyclic structure, as in, for example, succinimidyl,maleimidyl, and phthalimidyl:

Ureido: —N(R¹)CONR²R³ wherein R² and R³ are independently aminosubstituents, as defined for amino groups, and R¹ is a ureidosubstituent, for example, hydrogen, a C₁₋₇alkyl group, aC₃₋₂₀heterocyclyl group, or a C₃₋₂₀aryl group, preferably hydrogen or aC₁₋₇alkyl group. Examples of ureido groups include, but are not limitedto, —NHCONH₂, —NHCONHMe, —NHCONHEt, —NHCONMe₂, —NHCONEt₂, —NMeCONH₂,—NMeCONHMe, —NMeCONHEt, —NMeCONMe₂, —NMeCONEt₂ and —NHCONHPh.

Acyloxy (reverse ester): —OC(═O)R, wherein R is an acyloxy substituent,for example, a C₁₋₇ alkyl group, a C₃₋₂₀ heterocyclyl group, or a C₅₋₂₀aryl group, preferably a C₁₋₇ alkyl group. Examples of acyloxy groupsinclude, but are not limited to, —OC(═O)CH₃ (acetoxy), —OC(═O)CH₂CH₃,—OC(═O)C(CH₃)₃, —OC(═O)Ph, —OC(═O)C₆H₄F, and —OC(═O)CH₂Ph.

Thiol: —SH.

Thioether (sulfide): —SR, wherein R is a thioether substituent, forexample, a C₁₋₇ alkyl group (also referred to as a C₁₋₇ alkylthiogroup), a C₃₋₂₀ heterocyclyl group, or a C₅₋₂₀ aryl group, preferably aC₁₋₇ alkyl group. Examples of C₁₋₇ alkylthio groups include, but are notlimited to, —SCH₃ and —SCH₂CH₃.

Sulfoxide (sulfinyl): —S(═O)R, wherein R is a sulfoxide substituent, forexample, a C₁₋₇ alkyl group, a C₃₋₂₀ heterocyclyl group, or a C₅₋₂₀ arylgroup, preferably a C₁₋₇ alkyl group. Examples of sulfoxide groupsinclude, but are not limited to, —S(═O)CH₃ and —S(═O)CH₂CH₃.

Sulfonyl (sulfone): —S(═O)₂R, wherein R is a sulfone substituent, forexample, a C₁₋₇ alkyl group, a C₃₋₂₀ heterocyclyl group, or a C₅₋₂₀ arylgroup, preferably a C₁₋₇ alkyl group. Examples of sulfone groupsinclude, but are not limited to, —S(═O)₂CH₃ (methanesulfonyl, mesyl),—S(═O)₂CF₃, —S(═O)₂CH₂CH₃, and 4-methylphenylsulfonyl (tosyl).

Thioamido (thiocarbamyl): —C(═S)NR¹R², wherein R¹ and R² areindependently amino substituents, as defined for amino groups. Examplesof amido groups include, but are not limited to, —C(═S)NH₂, —C(═S)NHCH₃,—C(═S)N(CH₃)₂, and —C(═S)NHCH₂CH₃.

Sulfonamino: —NR¹S(═O)₂R, wherein R¹ is an amino substituent, as definedfor amino groups, and R is a sulfonamino substituent, for example, aC₁₋₇alkyl group, a C₃₋₂₀heterocyclyl group, or a C₅₋₂₀aryl group,preferably a C₁₋₇alkyl group. Examples of sulfonamino groups include,but are not limited to, —NHS(═O)₂CH₃, —NHS(═O)₂Ph and —N(CH₃)S(═O)₂C₆H₅.

As mentioned above, the groups that form the above listed substituentgroups, e.g. C₁₋₇ alkyl, C₃₋₂₀ heterocyclyl and C₅₋₂₀ aryl, maythemselves be substituted. Thus, the above definitions cover substituentgroups which are substituted.

Chemically Protected Forms

It may be convenient or desirable to prepare, purify, handle and/or usethe active compound in a chemically protected form. The term “chemicallyprotected form” is used herein in the conventional chemical sense andpertains to a compound in which one or more reactive functional groupsare protected from undesirable chemical reactions under specifiedconditions (e.g., pH, temperature, radiation, solvent, and the like). Inpractice, well known chemical methods are employed to reversibly renderunreactive a functional group, which otherwise would be reactive, underspecified conditions. In a chemically protected form, one or morereactive functional groups are in the form of a protected or protectinggroup (also known as a masked or masking group or a blocked or blockinggroup). By protecting a reactive functional group, reactions involvingother unprotected reactive functional groups can be performed, withoutaffecting the protected group; the protecting group may be removed,usually in a subsequent step, without substantially affecting theremainder of the molecule. See, for example, Protective Groups inOrganic Synthesis (T. Green and P. Wuts; 3rd Edition; John Wiley andSons, 1999).

Unless otherwise specified, a reference to a particular compound alsoincludes chemically protected forms thereof.

A wide variety of such “protecting,” “blocking,” or “masking” methodsare widely used and well known in organic synthesis. For example, acompound which has two nonequivalent reactive functional groups, both ofwhich would be reactive under specified conditions, may be derivatizedto render one of the functional groups “protected,” and thereforeunreactive, under the specified conditions; so protected, the compoundmay be used as a reactant which has effectively only one reactivefunctional group. After the desired reaction (involving the otherfunctional group) is complete, the protected group may be “deprotected”to return it to its original functionality.

For example, a hydroxy group may be protected as an ether (—OR) or anester (—OC(═O)R), for example, as: a t-butyl ether; a benzyl, benzhydryl(diphenylmethyl), or trityl (triphenylmethyl)ether; a trimethylsilyl ort-butyldimethylsilyl ether; or an acetyl ester (—OC(═O)CH₃, —OAc).

For example, an aldehyde or ketone group may be protected as an acetal(R—CH(OR)₂) or ketal (R₂C(OR)₂), respectively, in which the carbonylgroup (>C═O) is converted to a diether (>C(OR)₂), by reaction with, forexample, a primary alcohol. The aldehyde or ketone group is readilyregenerated by hydrolysis using a large excess of water in the presenceof acid.

For example, an amine group may be protected, for example, as an amide(—NRCO—R) or a urethane (—NRCO—OR), for example, as: a methyl amide(—NHCO—CH₃); a benzyloxy amide (—NHCO—OCH₂C₆H₅, —NH-Cbz); as a t-butoxyamide (—NHCO—OC(CH₃)₃, —NH-Boc); a 2-biphenyl-2-propoxy amide(—NHCO—OC(CH₃)₂C₆H₄C₆H₅, —NH-Bpoc), as a 9-fluorenylmethoxy amide(—NH-Fmoc), as a 6-nitroveratryloxy amide (—NH-Nvoc), as a2-trimethylsilylethyloxy amide (—NH-Teoc), as a 2,2,2-trichloroethyloxyamide (—NH-Troc), as an allyloxy amide (—NH-Alloc), as a2(-phenylsulphonyl)ethyloxy amide (—NH-Psec); or, in suitable cases(e.g., cyclic amines), as a nitroxide radical (>N—O.).

For example, a carboxylic acid group may be protected as an ester forexample, as: a C₁₋₇alkyl ester (e.g., a methyl ester; a t-butyl ester);a C₁₋₇haloalkyl ester (e.g., a C₁₋₇trihaloalkyl ester); atriC₁₋₇alkylsilyl-C₁₋₇alkyl ester; or a C₅₋₂₀aryl-C₁₋₇alkyl ester (e.g.,a benzyl ester; a nitrobenzyl ester); or as an amide, for example, as amethyl amide.

For example, a thiol group may be protected as a thioether (—SR), forexample, as: a benzyl thioether; an acetamidomethyl ether(—S—CH₂NHC(═O)CH₃).

In particular application in the present invention is the protection ofhydroxy and amino groups.

Catalysed Reactions

In one aspect of the present invention, there is provided a process forthe production of cyclic carbonates comprising contacting an epoxidewith carbon dioxide in the presence of a dimeric aluminium(acen) oraluminium(salacen) catalyst of formula I.

This reaction has the advantage that it may be carried out at easilyaccessible temperatures of between 0 and 40° C. and pressures of between0.5 and 2 atm. The reaction may even be carried out at temperatures ofbetween 0 and 140° C. and pressures of between 0.5 and 5 atm.Preferably, the reaction temperature lies between 20 and 30° C. Yieldsof over 50% may be achieved with short reaction times of 3 to 24 hours,using commercially viable amounts of catalyst, that is, from 0.1 to 10mol %, preferably 0.1 to 2.5 mol %. In some cases, yields of over 70% orover 90% may be achieved under these conditions.

The reaction may also be carried out in a flow reactor, wherein thereaction is continuous.

In some embodiments, the carbon dioxide may be supplied heated, and inother embodiments, the reaction may be heated by a conventional ormicrowave system.

In particular embodiments of the invention, there is provided a dimericaluminium catalyst of formula Ia:

wherein:

-   a) each of the substituents R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰,    R¹¹ and R¹², is independently selected from H, halo, optionally    substituted C₁₋₂₀ alkyl (including CAr₃, where Ar is a C₅₋₂₀ aryl    group), optionally substituted C₅₋₂₀ aryl, optionally substituted    C₃₋₂₀ heterocyclyl, ether and nitro; or-   b) R⁵ and R⁶ together with the carbon atoms to which they are    attached form an optionally substituted benzene ring of formula:

and

-   -   R¹¹ and R¹² together with the carbon atoms to which they are        attached form an optionally substituted benzene ring of formula:

-   -   each of the substituents R¹, R², R³, R⁴, R⁷, R⁸, R⁹, R¹⁰, R¹³,        R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰, is independently selected        from H, halo, optionally substituted C₁₋₂₀ alkyl (including        CAr₃, where Ar is a C₅₋₂₀ aryl group), optionally substituted        C₅₋₂₀ aryl, optionally substituted C₃₋₂₀ heterocyclyl, ether and        nitro;        X¹ and X² are independently either (i) a C₂₋₅ alkylene chain,        which is optionally substituted by one or more groups selected        from C₁₋₄ alkyl and C₅₋₇ aryl, or a C₁₋₃ bisoxyalkylene chain,        which is optionally substituted by one or more groups selected        from C₁₋₄ alkyl and O₅₋₇ aryl or (ii) represent a divalent group        selected from C₅₋₇ arylene, C₉₋₁₀ arylene, bi-C₅₋₇ aryl,        bi-C₉₋₁₀ aryl, C₅₋₇ cyclic alkylene and C₃₋₇ heterocyclylene,        which may be optionally substituted.

In particular embodiments of the invention, there is provided a catalystof formula (Ia) as defined above, except that:

-   (i) (a) at least one of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰,    R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰ (where present)    is selected from L-A, where L is a single bond or a C₁₋₁₀ alkylene    group and A is an onium group paired with a counterion selected from    Cl, Br and I; and/or    -   (b) at least one of X¹ and X² is a divalent C₃₋₇ heterocyclene        group, containing a ring atom which is a quaternary nitrogen        forming part of an ammonium group paired with a counterion        selected from Cl, Br and I; and/or    -   (c) at least one of X¹ and X² is a C₂₋₅ alkylene chain or a C₁₋₃        bisoxyalkylene chain, substituted by a group -Q-L-A, where Q is        either —C(═O)—O—, —C(═O)—NH—, or a single bond;        and/or-   (ii) (a) one of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹²,    R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰ (where present) is L-A′,    where L is as defined above and A′ is an onium linking group bound    to a solid support and paired with a counterion selected from Cl, Br    and I; or    -   (b) one of X¹ and X² is a divalent C₃₋₇ heterocyclene group,        containing a ring atom which is a quaternary nitrogen forming        part of an ammonium linking group bound to a solid support and        paired with a counterion selected from Cl, Br and I; or    -   (c) one of X¹ and X² is a C₂₋₅ alkylene chain or a C₁₋₃        bisoxyalkylene chain, substituted by a group -Q-L-A′.

In some aspects of the invention, L is selected from a single bond andC₁₋₇ alkylene.

In some embodiments of the invention, the aluminium(acen) or aluminium(salacen) catalyst of formula I or Ia is symmetrical, such that X¹═X²,R¹═R⁷, R²═R⁸, R³═R⁹, R⁴═R¹⁰, R⁵═R¹¹, R⁶═R¹² and (if present) R¹³═R¹⁷,R¹⁴═R¹⁸, R¹⁵═R¹⁹ and R¹⁶═R²⁰. In some embodiments, it is preferred thatR¹, R⁴, R⁷, and R¹⁹ are identical, R², R⁵, R⁸ and R¹¹ are identical, andR³, R⁶, R⁹, and R¹² are identical.

In the embodiments of the invention where the aluminium(acen) oraluminium (salacen) catalyst of formula I is symmetrical then thealkylene group formed by R² and R³ will be identical to that formed byR⁸ and R⁹, and the alkylene group formed by R⁵ and R⁶ will be identicalto that formed by R¹¹ and R¹², if these groups are present.

If the catalyst is covalently bound to a solid support, then it will notbe fully symmetrical.

In some embodiments, X¹ and X² are the same.

In some embodiments, X¹ and X² are independently selected from a C₂₋₅alkylene chain, which is preferably unsubstituted, and a C₁₋₃bisoxylakylene chain, which is preferably unsubstituted. These groupscan be represented as —(CH₂)_(n)— or —O—(CH₂)_(p)—O—, where n is 2, 3,4, or 5 and p is 1, 2, or 3. In these embodiments, n is preferably 2 or3 and p is preferably 1 or 2. n is more preferably 2. In theseembodiments X¹ and X² are preferably selected from —(CH₂)_(n)— (e.g.—C₂H₄—).

In other embodiments, X¹ and X² independently represent a divalent groupselected from C₅₋₇ arylene, C₉₋₁₀ arylene, bi-C₅₋₇ aryl, bi-C₃₋₁₀ aryl,C₅₋₇ cyclic alkylene and C₃₋₇ heterocyclylene, which may be optionallysubstituted. Preferably X¹ and X² independently represent C₅₋₇ cyclicalkylene, and more preferably C₆ cyclic alkylene. This group ispreferably saturated, and therefore is the group:

In other preferred embodiments, X¹ and X² independently represent C₅₋₇heterocyclene, and more preferably C₅ heterocyclene. One such preferredgroup is:

In this group, the nitrogen atom may be substituted, for example, by aC₁₋₄ alkyl group (e.g. methyl) that may itself be substituted, forexample, by a C₃₋₇ aryl group (e.g. phenyl). Therefore a preferred groupfor X¹ and X² is:

In other preferred embodiments, X¹ and X² independently represent C₅₋₇arylene, which is more preferably C₆ arylene, and in particular,benzylene:

When X¹ and X² independently represent a divalent group selected fromC₅₋₇ arylene, C₉₋₁₀ arylene, bi-C₅₋₇ aryl, bi-C₉₋₁₀ aryl, C₅₋₇ cyclicalkylene and C₃₋₇ heterocyclylene, they may preferably be unsubstituted.If they are substituted, then the substituents may be selected fromnitro, halo, C₁₋₄ alkyl, including substituted C₁₋₄ alkyl, (e.g. methyl,benzyl), C₁₋₄ alkoxy (e.g. methoxy) and hydroxy.

In some embodiments, R⁵ and R⁶, and R¹¹ and R¹² do not form fusedbenzene rings.

In some embodiments, R¹═R⁴═R⁷═R¹⁰=H.

In some embodiments, R³═R⁶═R⁹═R¹²=H.

In some embodiments, R¹═R⁴═R⁷═R¹⁰=Me.

In some embodiments, R³═R⁶═R⁹═R¹²=Me.

In some embodiments, R²═R⁵═R⁸═R¹¹=H.

In particularly preferred embodiments of the present invention,R¹═R⁴═R⁷═R¹⁰=Me; R³═R⁶═R⁹═R¹²=Me; and R²═R⁵═R⁸═R¹¹=H.

In some embodiments, R¹═R⁷=H.

In some embodiments, R²═R⁸=H.

In some embodiments, R³═R⁹=H.

In some embodiments, R⁴═R¹⁰=H.

In some embodiments, R⁵ and R⁶ together with the atoms to which they arejoined form a benzene ring, which is preferably unsubstituted.

In some embodiments, R¹¹ and R¹² together with the atoms to which theyare joined form a benzene ring, which is preferably unsubstituted.

In particularly preferred embodiments of the present invention, R¹═R⁷=H;R²═R⁸=H; R³═R⁹=H; R⁴═R¹⁰=H; R⁵ and R⁶ together with the atoms to whichthey are joined form an unsubstituted benzene ring; and R¹¹ and R¹²together with the atoms to which they are joined form an unsubstitutedbenzene ring.

If R², R⁵, R⁸ and R⁹ are selected from optionally substituted ester oroptionally substituted acyl, the ester group may be an unsubstitutedC₁₋₇ alkyl ester, more preferably an unsubstituted C₁₋₄ alkyl ester(e.g. ethyl ester), and the acyl group may be an unsubstituted C₁₋₇alkylacyl, more preferably an unsubstituted C₁₋₄ alkylacyl (e.g. methylacyl).

In further embodiments of the invention, R²═R⁵═R⁸═R¹¹=—CO₂Me. In theseembodiments, it may be preferred that R¹═R⁴═R⁷═R¹⁰=H, andR³═R⁶═R⁹═R¹²=Me. It may also or alternatively be preferred that X¹ andX² are —C₂H₄— or:

If a pair of R² and R³, R⁵ and R⁶, R⁸ and R⁹ and R¹¹ and R¹² togetherform a C₂₋₄ alkylene chain, the chain may be unsubstituted.

In some embodiments, it is one or more of R², R⁵, R⁸ and R¹¹ that is-L-A or L-A′. In some of these embodiments, if one of these groups is-L-A′, the other groups are -L-A. Alternatively, the other groups may be-L-A^(M), where A^(M) is a tertiary amine group, i.e. an amino groupwhere the amino substituents are both not hydrogen, for example, C₁₋₇alkyl (ethyl). The L in all these groups may be the same. In somefurther embodiments, one of R², R⁵, R⁸ and R¹¹ is -Q′-L-A or -Q′-L-A′.In some of these further embodiments, if one of these groups is-Q′-L-A′, the other groups are -Q′-L-A. Alternatively, the other groupsmay be -Q′-L-A^(M), where A^(M) is a tertiary amine group, i.e. an aminogroup where the amino substituents are both not hydrogen, for example,C₁₋₇ alkyl (ethyl). The L in all these groups may be the same. In someembodiments, those of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹²,R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰ (where present) which do notcomprise -L-A or -L-A′ are independently selected (where appropriate)from H, C₁₋₇ alkyl, ether and nitro. If none of the groups are -L-A or-L-A′ then they all may be independently selected (where appropriate)from H, C₁₋₇ alkyl, ether and nitro.

If a group selected from R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹,R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰ (where present) is ether,then the ether group is preferably a C₁₋₇ alkoxy group and morepreferably C₁₋₄ alkoxy group, e.g. methoxy.

If a group selected from R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹,R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰ (where present) is C₁₋₇alkyl, it may be C₁₋₄ alkyl, e.g. methyl, ethyl, propyl and butyl(preferably tert-butyl).

L is preferably unsubstituted.

L may preferably be a C₁₋₃ alkylene group, e.g. methylene, ethylene,propylene, and in some embodiments is methylene.

A may preferably be selected from ammonium groups, and in particular,those groups where R^(N1), R^(N2) and R^(N3) are independently selectedfrom C₁₋₇ alkyl groups and C₅₋₂₀ aryl groups, and where one or two ofR^(N1), R^(N2) and R^(N3) may also be H. Ammonium groups of particularinterest in the present invention include, but are not limited to,—NH(CH₃)₂, —NH(CH(CH₃)₂)₂, —N(CH₃)₃, —N(CH₂CH₃)₃, and —NH₂Ph.

A′ may preferably be selected from ammonium linking group, and inparticular those groups where R^(N1) and R^(N2) are independentlyselected from C₁₋₇ alkyl groups and C₅₋₂₀ aryl groups, where one or bothof R^(N1) and R^(N2) may also be H and where R^(N4) is a C₁₋₇ alkylenegroup. Ammonium linking groups of particular interest in the presentinvention include, but are not limited to, —NH(CH₃)(CH₂)—,—NH(CH(CH₃)₂)(C(CH₃)₂)—, —N(CH₃)₂(CH₂)—, —N(CH₂CH₃)₂(CH₂CH₂)—, and—NHPh(CH₂)—.

In some embodiments, Q may be —C(═O)—O— or —C(═O)—NH—.

When X′ and/or X² is substituted by -Q-L-A or -Q-L-A′, it is preferablya C₂ or C₃ alkylene group, more preferably a C₂ alkylene group, and maybe of the formula:

If X¹ or X² is a divalent C₃₋₇ heterocyclene group containing a ringatom which is a quaternary nitrogen atom, then it is preferably of theformula:

R^(N1) and R^(N2) in the above group are independently selected fromC₁₋₇alkyl groups (including, for example, those substituted by a C₆ arylgroup) and C₅₋₂₀ aryl groups, and where one of R^(N1) and R^(N2) mayalso be H. R^(N1) and R^(N2) groups of particular interest in abovestructure include, but are not limited to, —CH₃, —CH(CH₃)₂, and —CH₂Ph.

If X¹or X² is a divalent C₃₋₇ heterocyclene group containing a ring atomwhich is a quaternary nitrogen forming part of an ammonium linkinggroup, then it is preferably of the formula:

Compounds of particular interest are 6, 7, 10 and 11.

The reaction may be carried out under solvent-free conditions, dependingon the epoxides used. In some cases, the epoxides or the cycliccarbonates may act as a solvent for the catalyst. In particular, theinventors have found that propylene carbonate acts a suitable reactionsolvent.

Reactions using the catalyst of the first aspect, and some reactionsusing the catalyst of the second aspect, require the addition of aco-catalyst, Y⁻, and in particular MY, where M is a suitable cation,such as onium halides, which include, but are not limited to, R₄NY,R₃SY, R₄PY and R₄SbY, where each R is independently selected fromoptionally substituted C₁₋₁₀ alkyl, C₃₋₂₀ heterocyclyl and C₅₋₂₀ arylgroups and one R can be an acyl group, and simple halides, e.g. NaCl,Kl.

It is preferred that the co-catalyst for this reaction is of the formR₄NY, where each R is independently C₁₋₁₀ alkyl and Y is selected fromI, Br and Cl. R is preferably selected from C₃₋₅ alkyl, and morepreferably is butyl. Y is preferably Br. Therefore, a particularlypreferred co-catalyst is Bu₄NBr. The amount of co-catalyst is preferablyless than 2.5%, more preferably less than 1.0 mol % and most preferablyless than 0.5 mol %. In some embodiments using a catalyst of the secondaspect of the invention, no separate co-catalyst is present.

The above preferences may be combined with each other in any way that isappropriate.

Manufacture of dimeric aluminium(acen) and aluminium(salacen) Complexes

In a fourth aspect of the invention, there is provided a process for theproduction of dimeric aluminium(acen) and aluminium(salacen) catalystsof formula I.

When the catalyst of formula I comprises one or more onium group pairedwith a counterion, it may be synthesised from a precursor comprising thecorresponding neutral groups (e.g. amine, sulphide, phosphine) byreaction with a organic halide (i.e. a C₁₋₇ alkyl, C₃₋₂₀ heterocyclyl orC₅₋₂₀ aryl halide), or an organic group with another leaving group (e.g.tosylate).

When the catalyst of formula I comprises an onium linking group bound toa solid support, it may be synthesised from a precursor catalystcomprising a corresponding neutral group (e.g. amine, sulphide,phosphine) by reaction with a halide derived solid support or a solidsupport derived with another leaving group (e.g. tosylate).

In catalysts where at least one of R², R⁵, R⁸ and R⁹ are optionallysubstituted ester or optionally substituted acyl groups, the ligands maybe synthesised from precursors of formulae:

Such ligand synthesis is described, for example, in Yamada, et al.,Bull. Chem. Soc. Jpn., 80(7) (2007), 1391-1401.

In catalysts where at least one of the pairs of R² and R³, R⁵ and R⁶, R⁸and R⁹ and R¹¹ and R¹² are independently together form a C₂₋₄ alkylenechain, optionally substituted by one or more groups selected from C₁₋₄alkyl and C₅₋₇ aryl, or a C₁₋₃ bisoxyalkylene chain, which is optionallysubstituted by one or more groups selected from C₁₋₄ alkyl and C₅₋₇aryl, the ligands may be synthesised from precursors of formulae:

Such compounds are described, for example, in Barna and Robinson, TetLett 16 (1979), 1455-1458; Jones and Stokes, Tet 40(6) (1984),1051-1060; Kuhakarn, et al., Tet 61 (2005), 8995-9000; Martins, et al.,J Het Chem, 33 (1996), 1223-1231.

EXAMPLES General Experimental Methods IR Spectroscopy

IR spectra of liquids or of solids dissolved in a solvent were recordedbetween NaCl plates on a PE Spectrum 1 spectrometer. IR spectra of puresolids (ATR) were recorded on a Nicolet380 FTIR spectrometer fitted witha ‘Smart orbit’ attachment.

NMR

All NMR spectra were recorded at ambient temperature on a Bruker Avance300 spectrometer. The sample was dissolved in CDCl₃ unless specifiedotherwise.

Mass Spectroscopy

GCMS were recorded on a Varian CP-800-SATURN 2200 GC/MS ion-trap massspectrometer using a FactorFour (VF-5 ms) capillary column (30 m×0.25mm) with helium as the carrier gas. The conditions used were: initialtemperature 60° C., hold at initial temperature for 3 minutes then ramprate 15° C./min to 270° C.; hold at final temperature for 5 minutes. Forthe first 3.50 minutes, the eluent was routed away from the massdetector. Subsequently, the detector was operated in full El scan mode.Calibration was carried out by using a 50:50 mixture of pure isolatedcarbonate and reagent grade styrene oxide. Peak integration was found tobe virtually 50% for each component.

Low and high resolution electrospray spectra were recorded on a WatersLCT

Premier mass spectrometer.

Synthesis of Key Intermediates Acen Ligand (3)

Prepared by the method of McCarthy, P. J., et al., J. Am. Chem. Soc.,1955, 77, 5820. 1,2-Diaminoethane (1) (3.0 g, 3.3 mL, 49.9 mmol) wasdissolved in ethanol (70 mL) and acetylacetone (2) (10.3 mL, 99.8 mmol)was added in a steady stream over a period of about 10 minutes whilststirring the reaction mixture. The reaction was refluxed for 3 hours.After cooling, evaporation of the solvent in vacuo left a yellow solidwhich was purified by the addition of diethyl ether (ca. 100 mL). Thedesired ligand (3) (7.3 g, 32.4 mmol, 65%) was obtained as an off-whitecrystalline solid by suction filtration.

mp 116-118° C.

δ_(H)(CDCl₃) 4.97 (2H, s), 3.4-3.3 (4H, m), 1.97 (6H, s), 1.88 (6H, s)

Salacen Ligand (5)

Preparation based on the method reported by Phan, N. T. S., et al.,Dalton Trans., 2004, 1348. Ethylene diamine (1) (2.7 g, 45.0 mmol) wasdissolved in dichloromethane (50 mL) and salicylaldehyde (4) (5.0 g,41.0 mmol) was added in a slow stream while stirring the reaction. Theresulting yellow mixture was stirred at ambient temperature for afurther 30 minutes. Acetyl acetone (2) (4.5 g, 45.0 mmol) was then addedand the reaction mixture heated to reflux with stirring for one hour.The reaction was then allowed to cool to room temperature and wasstirred overnight. Evaporation of the solvent gave a yellow solid whichwas taken up in the minimum volume of hot methanol required to dissolveall the solids (ca. 10 mL) and then cooled. A yellow crystallineprecipitate formed which was filtered and identified as salen. Themother liquor was evaporated under vacuum to give the desired ligand (5)as a yellow/amber powder (2.7 g, 11.0 mmol, 27%).

Mp 122-126° C.

δ_(H)(CDCl₃) 8.35 (1H, s), 7.3-7.2 (2H, m), 7.0-6.9 (2H, m), 4.93 (1H,s), 3.75 (2H, m), 3.41 (2H, m), 1.99 (3H, s), 1.96 (3H, s).

Pyrrolidine-Based diamine acen Ligand (9)

Diamine 8 was prepared by the literature method (Hato, Y.; Kano, T.;Maruoka, K. Tetrahedron Letters, 2006, 8467) from the precursor diazidospecies by hydrogenation (10 atm H₂, 3.5 days) over 10% palladium oncarbon in ethanol (50 mL). The resulting product 8 (as a solution inethanol) was used directly with 2,4-pentanedione (0.3 mmol, 1.6 mL) andheated at reflux for 18 hours. The solvent was evaporated and theresulting residue taken up in dichloromethane (50 mL). The organicsolution was washed with water (3×20 mL) and brine (20 mL) and driedover sodium sulphate. Evaporation of the dichloromethane gave abeige/yellow solid 9 (0.30 g, 0.84 mmol, 62%). ¹H-NMR (CDCl₃) δ_(H):1.79-1.84 (2H, m), 1.91 (6H, s), 2.10 (6H, s), 2.74-2.79 (2H, m), 3.56(2H, s), 3.76 (2H, m), 4.82 (2H, m), 7.15-7.27 (5H, m). ¹³C-NMR δ_(C):18.6, 30.2, 53.6, 62.1, 65.8, 68.0, 127.1, 128.5, 129.0, 142.0, 157.3,204.2. m.p. 154-159° C.

Cyclohexane-Based diamine acen Ligand (14)

Compound 14 is disclosed in Pang, X., et al. Journal of OrganometallicChemistry 692 (2007) 5605-5613.

(R,R)-1,2-diaminocyclohexane dihydrochloride (13) (3.0 g, 16.0 mmol,)and sodium methoxide (1.7 g, 32.0 mmol) were added to a 1:1 mixture ofmethanol and ethanol (50 mL) and heated to reflux with stirring for 20minutes. Acetylacetone (2) (3.3 mL, 32.0 mmol) was then added and thereaction refluxed for 18 hours. The solvent was then evaporated in vacuoand the residue washed with diethyl ether (3×50 mL) to give the ligandas a pale yellow powder (3.6 g, 13.0 mmol, 81%).

Acen methyl ester Ligand (18)

Compound 14 is disclosed in Mukaiyama, T. et al. Chemistry Letters 1993,327-330. Methyl acetoacetate (15) (4.6 mL, 43.0 mmol) anddimethylformamide dimethylacetal (5.7 mL, 43.0 mmol) were stirred atambient temperature for two hours during which time the reaction turnedfrom colourless to orange. Then, a 2M aqueous solution of sodiumhydroxide (50 mL) was added and the reaction stirred for a further twohours during which time the solution became yellow. The reaction waspoured into a separating funnel and water (50 mL) and dichloromethane(50 mL) were added and the aqueous phase neutralized with 1M aqueoushydrochloric acid. The product was extracted using further washings ofdichloromethane (5×50 mL), dried with sodium sulphate, filtered andevaporated in vacuo. The resulting bright yellow oil (17) (6.0 g) becamered/orange on standing and was used directly in the next step withoutfurther purification.

The methyl 2-formyl 3-oxobutanoate (17) (6.0 g) was dissolved in ethanol(50 mL) and 1,2-diaminoethane (1) (1.4 mL, 21.5 mmol) was added. Ayellow precipitate formed immediately and the reaction was allowed tostir for one hour at ambient temperature. The solvent was thenevaporated in vacuo and the resulting material washed with diethyl ether(2×30 mL) to give the acen ligand (18) as a yellow powder (6.1 g, 20.0mmol, 91%). Mp>160° C. (decomp.), ν_(max)(ATR) 3400-2600 br, 3244 w,2955 w, 1702 s and 1622 cm⁻¹ s; ¹H NMR (CDCl₃): 11.06 (2H, br), 7.89(1H, s), 7.85 (1H, s), 3.70 (6H, s), 3.5-3.6 (4H, m), 2.46 (6H, s).

Cyclohexane-Based acen methyl ester Ligand (18)

(R,R)-1,2-diaminocyclohexane dihydrochloride (13) (3.0 g, 16.0 mmol) andsodium methoxide (1.7 g, 32.0 mmol) were added to a 1:1 mixture ofmethanol and ethanol (50 mL) and heated to reflux with stirring for 20minutes. Methyl 2-formyl 3-oxobutanoate (17) (4.6 g, 32.0 mmol) wasdissolved in ethanol (40 mL) and added to the refluxing solution ofdiamine. The reaction was allowed to stir under reflux for 20 hoursduring which time the solution became yellow. The solvent was thenevaporated in vacuo giving an orange gel which was rinsed with hexane(2×30 mL) to give the ligand as a yellow oil (5.1 g, 14.0 mmol, 87%).[α]_(D) ²³-524 (c=0.1, MeCN); ν_(max)(ATR) 3400-2400 br, 2943 m, 2864 m,1696 m and 1632 cm⁻¹ s; ¹H NMR (CDCl₃): 10.93 (2H, br), 8.31 (2H, br s),3.61 (6H, s), 3.1-3.3 (2H, m), 2.42 (6H, s), 1.9-1.7 (4H, m), 1.4-1.2(4H, m).

Example 1

Acen ligand (3) (1.0 g, 4.5 mmol) was dissolved in toluene (25 mL) andheated to reflux under a nitrogen atmosphere. Aluminium triethoxide (1.5g, 8.9 mmol) was then added and the reaction refluxed for 4 hours withstirring. The toluene was then removed by evaporation in vacuo and theresulting material taken up in dichloromethane (50 mL) and washed withwater (3×20 mL). Evaporation of the organic layer gave a yellow powderto which was added diethyl ether (30 mL). The desired complex (6) (1.0g, 2.0 mmol, 86%) was obtained as an off-white/light yellow crystallinesolid by suction filtration.

mp: decomp>270° C.

ν_(max)(ATR) 1605 (m), 1522 (s) and 1419 cm⁻¹ (m).

δ_(H)(CDCl₃) 5.11 (4H, s), 3.7-3.4 (8H, m), 2.03 (12H, s), 1.99 (12H,s).

δ_(C)(CDCl₃) 199.4, 177.4, 99.8, 46.2, 25.6, 21.7.

m/z (ES) 515.2 (MH⁺), 281.1.

Found: 515.2358, C₂₄H₃₇N₄O₅Al₂ (MH⁺) requires 515.2395.

Example 2

Salacen ligand (5) (1.0 g, 4.1 mmol) was dissolved in toluene (40 mL)and heated to reflux. Aluminium triethoxide (1.3 g, 8.3 mmol) was addedand the reaction refluxed for four hours under a nitrogen atmosphere.The solution was allowed to stir and cool to room temperature overnight.The solvent was evaporated under vacuum and the resulting material takenup in dichloromethane (50 mL) and washed with water (3×20 mL). Diethylether (ca. 25 mL) was added to the resulting residue after evaporationof the solvent. The flask was cooled in ice and a yellow precipitateformed and was collected by filtration to give the desired complex (7)as a light yellow solid (0.95 g, 1.7 mmol, 84%).

mp: decomp>230° C.

ν_(max)(ATR) 1637 (m), 1603 (m), 1526 (m), 1478 (m), 1455 (m) and 1408cm⁻¹ (w).

m/z (ES) 559.2 (MH⁺), 537.2, 581.2.

Found: 559.2083, C₂₈H₃₃N₄O₅Al₂ (MH⁺) requires 559.2082.

Example 3

Bimetallic aluminium(acen) complex (6) (22 mg, 0.043 mmol) was weighedinto a glass sample vial to which tetra-n-butyl ammonium bromide (TBAB)(13.5 mg, 0.042 mmol) was added. The vial was placed into a sealed flaskcontaining a second vial filled with solid CO₂ pellets. The pressure ofthe system was regulated with a balloon.

After saturation of the reaction vessel with CO₂ gas, styrene oxide (0.2g, 1.7 mmol) was added via a syringe to the catalyst-TBAB mixture. Thereaction was stirred at 30° C. for 24 hours. Samples were removed by asyringe and analysed by gas chromatography (or ¹H NMR spectroscopy)after 3 hours (33% conversion of styrene oxide to styrene carbonate), 6hours (52% conversion of styrene oxide to styrene carbonate) and 24hours (85% conversion of styrene oxide to styrene carbonate). After thistime was the reaction was worked up and an isolated yield of 81% wasobtained.

Styrene carbonate: mp 54-56° C. δ_(H)(CDCl₃) 7.4-7.3 (5H, m), 5.67 (1H,t J 8.0 Hz), 4.79 (1H, t J 8.3 Hz), 4.33 (1H, t J 8.0 Hz).

(ii) Using the same procedure with various epoxides, the followingresults were obtained with the aluminium(acen) complex (6) andaluminium(salacen) complex (7) and for comparison aluminium(salen)complex (C1) which was synthesised as follows:

Ethylenediamine (50 mmol, 3.3 mL) was added via a syringe to a stirredsolution of salicylaldehyde (100 mmol, 10.5 mL) in ethanol (100 mL). Ayellow precipitate formed immediately. The reaction mixture was refluxedfor 3 hours and the solvent was then removed in vacuo to leave a yellowcrystalline solid which was washed with diethyl ether (ca. 100 mL) togive salen ligand (C0) (12.0 g, 90%). Mp. 126-130° C. ¹H NMR 3.96 (4H,s, CH₂CH₂), 6.87 (2H, t J=8.4 Hz, 2×H_(Ar)), 6.97 (2H, t J=8.7 Hz,2×H_(Ar)), 7.2-7.3 (4H, m, 4×H_(Ar)), 8.38 (2H, s, 2×CH═N), 13.23 (2H,s, 2×OH).

Salen ligand (C0) (1.0 g, 3.9 mmol) and aluminium triethoxide (1.2 g,7.4 mmol) were dissolved in dry toluene (25 mL). The reaction mixturewas refluxed for 4 hours after which the toluene was evaporated and theresulting yellow residue taken up in dichloromethane and washed withwater (3×100 mL) and saturated brine (100 mL). After evaporation of theorganic phase, a light yellow powder was obtained which was washed withdiethyl ether (ca. 50 mL) and dried to give salen complex (C1) (1.2 g,49%). ¹H NMR 3.87 (8H, s, 2×CH₂CH₂), 6.7-6.9 (8H, m, 8×H_(Ar)), 7.1-7.3(8H, m, 8×H_(Ar)), 8.29 (4H, s, 4×CHN). ¹³C NMR 60.14, 65.09, 117.36,119.00, 131.81, 132.74, 161.46, 166.85. m/z (ESI) Found: 603.1775C₃₂H₂₅N₄O₅Al₂ (MH⁺), Requires 603.1769.

Substrate Conversion % Catalyst (R—) 3 h 6 h 24 h 6 Ph— 33 52   85(81)^(b) 7 60 72   93 C1 81 93  100 6 CH₃(CH₂)₃— 97 97  100 (94)^(b) 795 99  100 6 CH₃(CH₂)₇— 31 48   92 (89)^(b) 7 43 59   99 6 HOCH₂— 33 67  98 (90)^(b) 7 48 63  100 6 ClCH₂— 89 100  100 (91)^(b) 7 76 98  1006^(a) CH₃— 42 52   73 (70)^(b) 7^(a) 39 42   70 6^(c) H—  (58)^(b) 7^(c)(100)^(b) ^(a)Reaction was carried out at 0° C. ^(b)Isolated yield inbrackets. ^(c)Reactions were carried out in a stainless steel reactorwith CO₂ under pressure (<3 bar).

GC Retention Times:

Styrene oxide (7.35 mins), styrene carbonate (12.08 mins)

Hexene oxide (3.56 mins), hexene carbonate (9.80 mins)

Decene oxide (8.98 mins), decene carbonate (13.40 mins)

Propylene carbonate (5.26 mins)

Ethylene carbonate (5.98 mins)

NMR Data for carbonates: δ_(H)(CDCl₃):

1,2-Hexene carbonate: δ_(H)(CDCl₃) 4.65 (1H, m) 4.49 (1H, t J 7.6 Hz),4.01 (1H, t J 7.1 Hz), 1.7-1.6 (2H, m), 1.4-1.3 (4H, m), 0.89 (3H, t J6.6 Hz).

1,2-Decene carbonate: δ_(H)(CDCl₃) 4.7-4.6 (1H, m), 4.49 (1H, t J 8.1Hz), 4.03 (1H, t J 7.5 Hz), 1.24 (14H, m), 0.85 (3H, t J 6.6 Hz).

Propylene carbonate: δ_(H)(CDCl₃) 4.8-4.7 (1H, m), 4.55 (1H, t J 8.4Hz), 4.02 (1H, dd J 8.4, 7.3 Hz), 1.46 (3H, d J 6.3 Hz).

Glycidol carbonate: 4.8-4.7 (1H, m), 4.5-4.4 (2H, m), 4.00 (1H, dd J3.2, 12.9 Hz), 3.75 (1H, dd J 3.5, 12.7 Hz).

Epichlorohydrin carbonate: 5.0-4.9 (1H, m), 4.60 (1H, t J 8.7 Hz), 4.40(1H, dd J 8.7, 5.7 Hz), 3.8-3.6 (2H, m).

Example 4

Ligand 9 (0.84 mmol, 0.30 g) was dissolved in dry toluene (60 mL) andheated to reflux. Aluminium triethoxide (1.68 mmol, 0.27 g) was addedand heated for 24 hours. The resulting solution was washed with water(3×15 mL) and brine (15 mL) and dried over sodium sulphate. Evaporationyielded complex 10 as a yellow powder (0.32 mmol, 0.24 g, 75%). ¹H-NMR(CDCl₃) δ_(H): 1.78-1.85 (4H, m), 2.08 (12H, s), 2.11 (12H, s),2.73-2.79 (4H, m), 3.58 (4H, s), 3.78 (2H, m), 4.51 (2H, m), 7.15-7.26(10H, m). ¹³C-NMR δ_(C): 19.6, 25.7, 62.1, 65.7, 67.6, 109.0, 127.1,128.5, 129.0, 142.0, 155.8, 164.6. m.p. decomp>210° C. m/z (ES) 381.2(MH⁺), 412.2 (OCH₃H⁺). HRMS (ESI): MH⁺ (C₂₁H₂₈N₃O₂Al⁺) 381.1997. found381.2011.

Example 5

Complex 10 (0.13 mmol, 0.1 g) was dissolved in acetonitrile (5 mL) andbenzyl bromide was added (6 eq., 0.8 mmol, 0.1 mL). The resultingmixture was heated to reflux and stirred for 24 hours during which timea dark orange precipitate formed. After cooling, the solvent wasevaporated and the resulting material taken up in ether (ca. 20 mL) andfiltered yielding 11 as a yellow/orange solid.

Example 6

(i) Complex 10 was used as a catalyst in the method of Example 3(i), andhad a yield of 6% at 24 hours.

(ii) Complex 11 was used as a catalyst in the method of Example 3(i),except for the absence of the TBAB cocatalyst. The yield was 5% after 24hours.

Example 7

(R,R)-Cyclohexanediamine acen ligand (14) (3.0 g, 11.0 mmol) was addedto a 5:1 dry toluene/acetonitrile solution (60 mL). Aluminiumtriethoxide (2.1 g, 13.0 mmol) was then added and the reaction refluxedfor 20 hours. The solvent was evaporated in vacuo and the residue takenup in dichloromethane (80 mL). The resulting slurry was washed withwater (3×50 mL) and saturated brine (50 mL). The organic phase was thendried over sodium sulphate, filtered and evaporated in vacuo. Theresidue was rinsed with diethyl ether (ca. 30 mL) and dried in vacuo foran hour to give the aluminium complex (20) as a pale yellow powder (0.54g, 0.86 mmol, 16%). Mp>170° C. (decomp.), [α]_(D) ²³-688 (c=0.1, MeCN),ν_(max)(ATR) 2931 w, 2859 w, 1606 s and 1577 cm⁻¹ s; ¹H NMR (CDCl₃):4.89 (2H, s), 3.1-3.2 (2H, m), 1.98 (6H, s), 1.83 (6H, s), 2.0-1.7 (4H,m), 1.5-1.2 (4H, m).

Example 8

Acen methyl ester ligand (18) (3.0 g, 10.0 mmol) was added to drytoluene and the mixture was heated to reflux to dissolve the ligand.Aluminium triethoxide (1.9 g, 12.0 mmol) was added and the reactionrefluxed for 20 hours. The solvent was removed in vacuo, taken up indichloromethane (50 mL) and washed with water (3×20 mL) and brine (20mL). The organic phase was dried over sodium sulphate and evaporated invacuo. The residue was dried in vacuo to give the aluminium complex (21)as a pale yellow powder (3.2 g, 4.6 mmol, 92%). Mp 188-190° C.,ν_(max)(ATR) 2949 w, 1695 m and 1616 cm⁻¹ s; ¹H NMR (CDCl₃): 8.31 (1H,s), 8.09 (1H, s), 3.73 (4H, br, s), 3.69 (6H, s), 2.40 (6H, s); m/z(ESI, MeOH) 705 (M+Me)⁺, 691 MH⁺.

Example 9

(R,R)-Cyclohexanediamine acen methyl ester (19) (3.0 g, 8.2 mmol) wasadded to dry toluene and the mixture was heated to reflux to dissolvethe ligand. Aluminium triethoxide (2.7 g, 16.0 mmol) was added and thereaction refluxed for 22 hours. The solvent was removed in vacuo and theresidue taken up in dichloromethane (50 mL) and washed with water (3×20mL) and brine (20 mL). The organic phase was dried over sodium sulphateand evaporated in vacuo. The residue was dried in vacuo to give thealuminium complex (22) as a pale yellow powder (2.9 g, 3.6 mmol, 89%).[α]_(D) ²³-488 (c=0.1, MeCN), ¹H NMR (CDCl₃): 8.4-7.8 (4H, m), 3.5-3.4(16H, m), 2.24 (12H, s), 1.9-1.4 (8H, m), 1.2-0.8 (8H, m).

Example 10

Complexes 20, 21 and 22 were used as a catalyst in the method of Example3(i), and had yields as shown in the table below:

Conversion % Catalyst 3 h 6 h 24 h 20 2 6 16 21 7 15 36 22 3 6 15

1. A dimeric aluminium catalyst of formula I:

wherein: a) each of the substituents R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹,R¹⁰, R¹¹ and R¹², is independently selected from H, halo, optionallysubstituted C₁₋₂₀ alkyl, optionally substituted C₅₋₂₀ aryl, optionallysubstituted C₃₋₂₀ heterocyclyl, ether and nitro, where R², R⁵, R⁸ andR¹¹ may additionally be independently selected from optionallysubstituted ester or optionally substituted acyl or the pairs of R² andR³, R⁵ and R⁶, R⁸ and R⁹ and R¹¹ and R¹² may independently together forma C₂₋₄ alkylene chain, optionally substituted by one or more groupsselected from C₁₋₄ alkyl and C₅₋₇ aryl; or b) R⁵ and R⁶ together withthe carbon atoms to which they are attached form an optionallysubstituted benzene ring of formula:

and R¹¹ and R¹² together with the carbon atoms to which they areattached form an optionally substituted benzene ring of formula:

each of the substituents R¹, R², R³, R⁴, R⁷, R⁸, R⁹, R¹⁰, R¹³, R¹⁴, R¹⁵,R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰, is independently selected from H, halo,optionally substituted C₁₋₂₀ alkyl, optionally substituted C₅₋₂₀ aryl,optionally substituted C₃₋₂₀ heterocyclyl, ether and nitro; X¹ and X²are independently either (i) a C₂₋₅ alkylene chain, which is optionallysubstituted by one or more groups selected from C₁₋₄ alkyl and C₅₋₇aryl, or a C₁₋₃ bisoxyalkylene chain, which is optionally substituted byone or more groups selected from C₁₋₄ alkyl and C₅₋₇ aryl or (ii)represent a divalent group selected from C₅₋₇ arylene, C₉₋₁₀ arylene,bi-C₅₋₇ aryl, bi-C₉₋₁₀ aryl, C₅₋₇ cyclic alkylene and C₃₋₇heterocyclylene, which may be optionally substituted.
 2. A catalystaccording to claim 1, wherein: (a) X¹ and X² are independently selectedfrom an unsubstituted C₂₋₅ alkylene chain and an unsubstituted C₁₋₃bisoxylakylene chain; or (b) X¹ and X² independently represent C₅₋₇cyclic alkylene.
 3. (canceled)
 4. A catalyst according to claim 1,wherein X¹ and X² are the same.
 5. A catalyst according to claim 1,wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴,R¹⁵R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰, where present, are independentlyselected, from H, C₁₋₇ alkyl, ether and nitro.
 6. A catalyst accordingto any one of claims 1, 2, 4, or 5, wherein: (a) R¹═R⁴═R⁷═R¹⁰=H orR¹═R⁴═R⁷═R¹⁰=Me; and/or (b) R³═R⁶═R⁹═R¹² ═H or R³=R⁶═R⁹═R¹²=Me; and/or(c) R⁵ and R⁶, and R¹¹ and R¹²; and/or (d) R⁵ and R⁶, and R¹¹ and R¹² donot form fused benzene rings.
 7. (canceled)
 8. (canceled)
 9. (canceled)10. (canceled)
 11. (canceled)
 12. A catalyst according to any one ofclaims 1, 2, 4, 5, or 6, wherein the catalyst is immobilized on a solidsupport, either by the use of steric effects or by electrostaticbinding.
 13. A dimeric aluminium catalyst of formula I:

wherein: a) each of the substituents R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹,R¹⁰, R¹¹ and R¹², is independently selected from H, halo, optionallysubstituted C₁₋₂₀ alkyl, optionally substituted C₅₋₂₀ aryl, optionallysubstituted C₃₋₂₀ heterocyclyl, ether and nitro, where R², R⁵, R⁸ andR¹¹ may additionally be independently selected from optionallysubstituted ester or optionally substituted acyl or the pairs of R² andR³, R⁵ and R⁶, R⁸ and R⁹ and R¹¹ and R¹² may independently together forma C₂₋₄ alkylene chain, optionally substituted by one or more groupsselected from C₁₋₄ alkyl and C₅₋₇ aryl; or b) R⁵ and R⁶ together withthe carbon atoms to which they are attached form an optionallysubstituted benzene ring of formula:

and R¹¹ and R¹² together with the carbon atoms to which they areattached form an optionally substituted benzene ring of formula:

each of the substituents R¹, R², R³, R⁴, R⁷, R⁸, R⁹, R¹⁰, R¹³, R¹⁴, R¹⁵,R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰, is independently selected from H, halo,optionally substituted C₁₋₂₀ alkyl (including CAr₃, where Ar is a C₅₋₂₀aryl group), optionally substituted C₅₋₂₀ aryl, optionally substitutedC₃₋₂₀ heterocyclyl, ether and nitro; X¹ and X² are independently either(i) a C₂₋₅ alkylene chain, which is optionally substituted by one ormore groups selected from C₁₋₄ alkyl and C₅₋₇ aryl, or a C₁₋₃bisoxyalkylene chain, which is optionally substituted by one or moregroups selected from C₁₋₄ alkyl and C₅₋₇ aryl or (ii) represent adivalent group selected from C₅₋₇ arylene, C₉₋₁₀ arylene, bi-C₅₋₇ aryl,bi-C₉₋₁₀ aryl, C₅₋₇ cyclic alkylene and C₃₋₇ heterocyclylene, which maybe optionally substituted, wherein: (i) (a) at least one of R¹, R², R³,R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹and R²⁰ (where present) is selected from L-A, where L is a single bondor a C₁₋₁₀ alkylene group and A is an onium group paired with acounterion selected from Cl, Br and I; and/or (b) at least one of X¹ andX² is a divalent C₃₋₇ heterocyclene group, containing a ring atom whichis a quaternary nitrogen forming part of an ammonium group paired with acounterion selected from Cl, Br and I; and/or (c) at least one of X¹ andX² is a C₂₋₅ alkylene chain or a C₁₋₃ bisoxyalkylene chain, substitutedby a group -Q-L-A, where Q is either —C(═O)—O—, —C(═O)—NH—, or a singlebond; and/or (d) at least one of R², R⁵, R⁸ and R¹¹ is -Q′-L-A, where Q′is either —C(═O)—O— or —C(═O)—; and/or (ii) (a) one of R¹, R², R³, R⁴,R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹ andR²⁰ (where present) is L-A′, where L is as defined above and A′ is anonium linking group bound to a solid support and paired with acounterion selected from Cl, Br and I; or (b) one of X¹ and X² is adivalent C₃₋₇ heterocyclene group, containing a ring atom which is aquaternary nitrogen forming part of an ammonium linking group bound to asolid support and paired with a counterion selected from Cl, Br and I;or (c) one of X¹ and X² is a C₂₋₅ alkylene chain or a C₁₋₃bisoxyalkylene chain, substituted by a group -Q-L-A′; or (d) one of R²,R⁵, R⁸ and R¹¹ is -Q′-L-A′.
 14. A catalyst according to claim 13,wherein X¹ and X² are independently selected from an unsubstituted C₂₋₅alkylene chain and an unsubstituted C₁₋₃ bisoxylakylene chain.
 15. Acatalyst according to claim 13, wherein X¹ and X² are the same.
 16. Acatalyst according to claim 13, wherein those of R¹, R², R³, R⁴, R⁵, R⁶,R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰(where present) which do not comprise -L-A or -L-A′ are independentlyselected (where appropriate) from H, C₁₋₇ alkyl, ether and nitro.
 17. Acatalyst according to claim 13, wherein: (a) R¹═R⁴═R⁷═R¹⁰═H; and/or (b)R³═R⁶═R⁹═R¹²═H; and/or (c) R⁵ and R⁶, and R¹¹ and R¹² do not form fusedbenzene rings.
 18. (canceled)
 19. (canceled)
 20. A catalyst according toclaim 13, wherein L is an unsubstituted C₁₋₃ alkylene group.
 21. Acatalyst according to claim 13, wherein one of R¹, R², R³, R⁴, R⁵, R⁶,R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹ and R²⁰(where present) is selected from L-A′ and A′ is selected from—NH(CH₃)(CH₂)—, —NH(CH(CH₃)₂)(C(CH₃)₂)—, —N(CH₃)₂(CH₂)—,—N(CH₂CH₃)₂(CH₂CH₂)—, and —NHPh(CH₂)—.
 22. A catalyst according to claim13, wherein: X¹ or X² is substituted by -Q-L-A′ and is of formula:

or (b) X¹ or X² is a divalent C₃₋₇ heterocyclene group containing a ringatom which is a quaternary nitrogen forming part of an ammonium linkinggroup, and is of formula:

where R^(N1) is selected from H, C₁₋₇ alkyl and C₅₋₂₀ aryl and whereR^(N4) is a C₁₋₇alkylene group.
 23. (canceled)
 24. A catalyst accordingto claim 13, wherein the ammonium counter group is Br⁻.
 25. A processfor the production of cyclic carbonates comprising contacting an epoxidewith carbon dioxide in the presence of a catalyst according to claim 1in combination with a co-catalyst capable of supplying Y⁻, where Y isselected from Cl, Br and I.
 26. The process of claim 25, wherein thecatalysed reaction is:

wherein R^(C3) and R^(C4) are independently selected from H, optionallysubstituted C₁₋₁₀ alkyl, optionally substituted C₃₋₂₀ heterocyclyl andoptionally substituted C₅₋₂₀ aryl, or R^(C3) and R^(C4) form anoptionally substituted linking group between the two carbon atoms towhich they are respectively attached.
 27. (canceled)
 28. (canceled) 29.(canceled)
 30. A process for the production of cyclic carbonatescomprising contacting an epoxide with carbon dioxide in the presence ofa catalyst according to claim
 13. 31. The process of claim 18, whereinthe catalysed reaction is:

wherein RC3 and RC4 are independently selected from H, optionallysubstituted C1-10 alkyl, optionally substituted C3-20 heterocyclyl andoptionally substituted C5-20 aryl, or RC3 and RC4 form an optionallysubstituted linking group between the two carbon atoms to which they arerespectively attached.